title: p16INK4A immunohistochemical staining and predictive value for progression of cervical intraepithelial neoplasia grade 1: a prospective study in China.
abstract: p16(INK4A) is strongly expressed in tissues diagnosed as cervical intraepithelial neoplasia (CIN) and cancer in women infected with human papillomavirus (HPV), but few prospective studies have evaluated p16(INK4A) as a marker for the risk of low-grade CIN (CIN1) progression. We investigated the prevalence of p16(INK4A) immunostaining by CIN grade and whether overexpression of p16(INK4A) in CIN1 predicts future risk for high-grade CIN in Chinese women. 6,557 Chinese women aged 30-49 years were screened from 2003 to 2005 using cytology and carcinogenic HPV test. Colposcopy was performed on women with any abnormal result. p16(INK4A) Immunostaining was performed on biopsies from all women with CIN1, as well as randomly selected women with normal or CIN grade 2 and worse (CIN2+) biopsies. Women with CIN1 were followed up without treatment. Colposcopy was performed on all untreated women at a 2-year interval. The prevalence of p16(INK4A) staining was 2.7%, 42.7%, 75.5%, 79.6% and 100% among women with normal, CIN1, 2, 3 and cancer biopsies, respectively (p < 0.001). HPV positivity was strongly associated with p16(INK4A) staining [odds ratios (OR) = 12.8; 95% confidence intervals (CI): 5.2-31.6]. p16(INK4A) staining of CIN1 biopsies at baseline was associated with an increased risk of finding high-grade CIN over 2 years of follow-up (OR = 1.43; 95% CI: 0.52-3.91). The two-year cumulative incidence of CIN2+ for p16(INK4A) positive women was higher at 10.71% than for p16(INK4A) negative women at 1.30% (crude RR = 8.25, 95% CI: 1.02-66.62). p16(INK4A) overexpression is strongly associated with grade of CIN and risk of progression to high-grade CIN in women with low-grade lesions.
authors.affiliation: Department of Gynecology and Obstetrics, The West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China; Department of Cancer Epidemiology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Guang-Dong
authors.initials: GD
authors.lastname: Liao
authors.forename: John W
authors.initials: JW
authors.lastname: Sellors
authors.forename: Hai-Kui
authors.initials: HK
authors.lastname: Sun
authors.forename: Xun
authors.initials: X
authors.lastname: Zhang
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Bao
authors.forename: Jose
authors.initials: J
authors.lastname: Jeronimo
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Fang-Hui
authors.initials: FH
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.forename: Zhi
authors.initials: Z
authors.lastname: Cao
authors.forename: Shao-Kai
authors.initials: SK
authors.lastname: Zhang
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Xi
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Qiao
mesh_terms: D000328:Adult; D001706:Biopsy / Q000379:methods; D002681:China; D003127:Colposcopy / Q000379:methods; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000821:virology; D011446:Prospective Studies; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000821:virology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: biomarker; cervical intraepithelial neoplasia; p16INK4A; predictive validity; prospective study